Friday, April 18, 2014

Tranexamic acid--why you may be less likely to bleed to death in Britain than the U.S.

The other day at an interdisciplinary rounds meeting at the hospital, one of our nurses who is also an emergency medical technician mentioned that in Britain injured patients receive tranexamic acid before arriving at the hospital because it reduces death from bleeding. “What’s that?” I said. I kind of barely remembered hearing this medication’s name associated with the treatment of a rare disease, but not treatment of trauma. So I was guessing that this was some drug that was invented long ago which had been found to be quite effective in other countries, but has not been really optimally used in the U.S. because it is generic and therefore unlikely to make drug companies money.

Bingo.

Here’s the story, as far as I can determine.

Tranexamic acid is a relatively simple cyclic molecule that blocks the fibrinolytic process, that is, the natural breakdown of blood clots in the body. In the setting of any injury, especially severe ones, fibrinolysis is intensified, leading to a condition of excess bleeding in trauma victims. This is hardly ideal, and tranexamic acid can help reverse this. It also appears to have an effect on reducing inflammation, which may be even more significant.

There have been a couple of major studies in the last 3 years showing significantly better outcomes in patients who have traumatic injury and who are treated with tranexamic acid intravenously soon after injury. The most recent study, published in the Archives of Surgery, looked at 896 patients injured in the military from registries in the UK and the U.S. and identified the subset treated with tranexamic acid. Although this group was generally more severely injured, the mortality rate was significantly lower, 6.5% lower, than the group that had not received the drug. In very seriously injured patients, those who received massive transfusion of blood products, the difference in survival was nearly 14%.

It is not often that we see an effect this powerful, especially in a group like this who are healthy and will likely have long and productive lives after being saved. An earlier study, published in 2011 in the Lancet titled CRASH-2, showed similar results in civilian trauma victims, with a double-blind, prospective design. The Cochrane Collaboration, a group of researchers who review randomized controlled trials, concluded that tranexamic acid was safe and effective in reducing mortality in trauma patients without increasing adverse events.

So maybe it’s actually very expensive, then. I called our hospital pharmacy to ask about that. Apparently a gram of it costs about $44. The usual protocol for trauma is 1 gram intravenously right away and then another gram over the next 8 hours. So $88 times 100 equals $8,800 to save 6.5 lives (using the data from the military study), or $1,353 per life saved. That’s pretty cheap. And since it probably reduces the severity of illness in the rest of the patients treated, it may end up reducing overall treatment costs.

Presently the only FDA (Food and Drug Administration) approved indication for this drug in the U.S. is an oral formulation to be used for women with heavy periods and intravenously for prevention of dental bleeding in hemophiliacs. It is also used off-label to reduce transfusion requirements in total joint surgeries (that’s why we have it in our pharmacy), also in some places for prostate surgery, general surgery, gastrointestinal hemorrhage, bleeding around pregnancy and delivery and bleeding within the eye. It reduces the frequency of attacks of swelling in a condition called hereditary angioedema, which is rare, and was why I had even heard of it in the past. It has been available over the counter for years in Europe, marketed for heavy menstrual bleeding. The injectable formulation is also on the World Health Organization’s list of 350 essential medicines which are considered safe and effective and necessary worldwide.

So what are its side effects? It may increase the risk of blood clots in the legs and lungs, but studies have shown this to be far less of an issue than one might guess, and it looks like the lives saved far outweigh this risk. The CRASH-2 study showed that there might be a slight risk of increasing mortality if it was given to trauma patients more than 3 hours after their injury.

Why is it not FDA approved for reduction of bleeding in trauma and other similar situations for which there is ample evidence of safety and efficacy? The FDA approves drugs and devices when approval is requested, and usually the drug or device manufacturers who stand to make money from an FDA approved indication are the ones to make the request. I suspect there has been no request for approval for these other indications. Just because it is not FDA approved to reduce bleeding in trauma and surgery doesn’t mean it can’t be used, but physicians have a certain hesitance to use unfamiliar drugs off-label.

So the story of tranexamic acid is another excellent example of how simpler, cheaper and sometimes more effective treatments are not being widely used in the U.S., even though our patients may receive exorbitantly expensive medications and treatments of dubious or minimal benefit. This is because we allow powerful pharmaceutical companies to inform our practice. Sometimes this actually works, when companies produce groundbreaking innovations and encourage us to adopt them. It is unlikely, though, to help us find creative uses for inexpensive drugs that have been around a long time. This dynamic may mean that 6 or so people of the 100 who are probably just now being involved in accidents with bleeding will die when they would not have if use of this drug part of our routine practice.

Janice Boughton, MD, ACP Member, practiced in the Seattle area for four years and in rural Idaho for 17 years before deciding to take a few years off to see more places, learn more about medicine and increase her knowledge base and perspective by practicing hospital and primary care medicine as a locum tenens physician. She lives in Idaho when not traveling. Disturbed by various aspects of the practice of medicine that make no sense and concerned about the cost of providing health care to every American, she blogs at Why is American Health Care So Expensive?, where this post originally appeared.

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Albert Fuchs,
MD
Albert Fuchs, MD, FACP, graduated from the
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And Thus, It Begins
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she which chronicles her journey through medical training from day
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Auscultation Ira S. Nash,
MD, FACP, is the senior vice president and executive director of the North Shore-LIJ
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Zackary Berger
Zackary Berger, MD, ACP Member, is a primary care doctor and
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communication, bioethics, and systematic reviews.

Controversies in Hospital
Infection Prevention
Run by three ACP
Fellows, this blog ponders vexing issues in infection prevention
and control, inside and outside the hospital. Daniel J Diekema, MD,
FACP, practices infectious diseases, clinical microbiology, and
hospital epidemiology in Iowa City, Iowa, splitting time between
seeing patients with infectious diseases, diagnosing infections in
the microbiology laboratory, and trying to prevent infections in
the hospital. Michael B. Edmond, MD, FACP, is a hospital
epidemiologist in Iowa City, IA, with a focus on understanding why
infections occur in the hospital and ways to prevent these
infections, and sees patients in the inpatient and outpatient
settings. Eli N. Perencevich, MD, ACP Member, is an infectious
disease physician and epidemiologist in Iowa City, Iowa, who
studies methods to halt the spread of resistant bacteria in our
hospitals (including novel ways to get everyone to wash their
hands).

Suneel Dhand, MD, ACP Member Suneel Dhand, MD,
ACP Member, is a practicing physician in Massachusetts. He has published numerous
articles in clinical medicine, covering a wide range of specialty areas including;
pulmonology, cardiology, endocrinology, hematology, and infectious disease. He has also
authored chapters in the prestigious "5-Minute Clinical Consult" medical textbook. His
other clinical interests include quality improvement, hospital safety, hospital
utilization, and the use of technology in health care.

Dr. Mintz' Blog
Matthew Mintz, MD, FACP, has practiced internal medicine for more
than a decade and is an Associate Professor of Medicine at an
academic medical center on the East Coast. His time is split
between teaching medical students and residents, and caring for
patients.

FutureDocs
Vineet Arora, MD, FACP, is Associate Program Director for the
Internal Medicine Residency and Assistant Dean of Scholarship &
Discovery at the Pritzker School of Medicine for the University of
Chicago. Her education and research focus is on resident duty
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hospital care. She is also an academic hospitalist.

Glass Hospital
John H. Schumann, MD, FACP, provides transparency on the workings
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Gut Check
Ryan Madanick, MD, ACP Member, is a gastroenterologist at the
University of North Carolina School of Medicine, and the Program
Director for the GI & Hepatology Fellowship Program. He
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the diagnosis and treatment of patients who have
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heartburn, and chest pain.

David Katz, MD
David L. Katz, MD, MPH, FACP, is an internationally renowned
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Just Oncology
Richard Just, MD, ACP Member, has 36 years in clinical practice of
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Medical Lessons
Elaine Schattner, MD, FACP, shares her ideas on education, ethics
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Mired in MedEd
Alexander M.
Djuricich, MD, FACP, is the Associate Dean for Continuing Medical
Education (CME), and a Program Director in Medicine-Pediatrics at
the Indiana University School of Medicine in Indianapolis, where he
blogs about medical education.

More Musings
Rob Lamberts, MD, ACP Member, a med-peds and general practice
internist, returns with "volume 2" of his personal musings about
medicine, life, armadillos and Sasquatch at More Musings (of a
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Prescriptions
David M. Sack, MD, FACP, practices general gastroenterology at a
small community hospital in Connecticut. His blog is a series of
musings on medicine, medical care, the health care system and
medical ethics, in no particular order.

The Blog of Paul Sufka
Paul Sufka,
MD, ACP Member, is a board certified rheumatologist in St. Paul,
Minn. He was a chief resident in internal medicine with the
University of Minnesota and then completed his fellowship training
in rheumatology in June 2011 at the University of Minnesota
Department of Rheumatology. His interests include the use of
technology in medicine.

Technology in (Medical)
Education
Neil Mehta, MBBS, MS, FACP, is interested in use of technology in
education, social media and networking, practice management and
evidence-based medicine tools, personal information and knowledge
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Peter A. Lipson,
MD
Peter A. Lipson, MD, ACP Member, is a practicing internist and
teaching physician in Southeast Michigan. The blog, which has been
around in various forms since 2007, offers musings on the
intersection of science, medicine, and culture.

Why is American Health Care So Expensive?
Janice
Boughton, MD, FACP, practiced internal medicine for 20 years before
adopting a career in hospital and primary care medicine as a locum
tenens physician. She lives in Idaho when not traveling.

World's Best Site
Daniel Ginsberg, MD,
FACP, is an internal medicine physician who has avidly applied
computers to medicine since 1986, when he first wrote medically
oriented computer programs. He is in practice in Tacoma,
Washington.

Other
blogs of note:

American Journal of
Medicine
Also known as the Green Journal, the American Journal of Medicine
publishes original clinical articles of interest to physicians in
internal medicine and its subspecialities, both in academia and
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Interact MD
Michael Benjamin, MD, ACP member, doesn't accept industry money so
he can create an independent, clinician-reviewed space on the
Internet for physicians to report and comment on the medical news
of the day.

PLoS Blog
The Public Library of Science's open access materials include a
blog.

White Coat
Rants
One of the most popular anonymous blogs written by an emergency
room physician.

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